Abstract
The human brain maintains billions of neurons functional across the lifespan of the individual. The glial, supportive cells of the brain are indispensable to neuron elasticity. They undergo various states (active, reactive, macrophage, primed, resting) and carefully impose either quick repair or the cleaning of injured neurons to avoid damage extension. Identifying the failure of these interactions involving the relation of the input of glial cells to the inception and/or progression of chronic neurodegenerative diseases (ND) is crucial in identifying therapeutic options, given the well-built neuro-immune module of these diseases. In the present review, we scrutinize different interactions and important factors including direct cell–cell contact, intervention by the CD200 system, various receptors present on their surfaces, CXC3RI and TREM2, and chemokines and cytokines with special reference to Alzheimer’s disease (AD). The present review of the available literature will elucidate the contribution of microglia and astrocytes to the pathophysiology of AD, thus evidencing glial cells as obligatory transducers of pathology and superlative targets for interference.
Highlights
Received: 22 November 2021Neuron–glia crosstalk has been an appealing issue for neuroscientists around the globe due to escalating conditions of neurodegenerative diseases in the elderly population [1].Neurodegenerative disease comprises both systems of the body, i.e., the central and peripheral nervous system
This homeostatic microglial function is supported by neuronal immunomodulators like CX3CL1 and CD200, which act as the ligand for their receptors located on microglia
CXC3CR1 is associated with the transcriptomic signature status of microglial cells depicting normal conditions, but in Alzheimer’s disease (AD) pathology, the downregulation of CXC3R1 has been reported recently, revealing disturbances in the homeostasis of the central nervous system (CNS) [38,50,51,52,53,54]
Summary
Neuron–glia crosstalk has been an appealing issue for neuroscientists around the globe due to escalating conditions of neurodegenerative diseases in the elderly population [1]. The importance of alterations in synergistic interactions between cells (neurons, microglia, and astrocytes) in the pathogenesis of this neurodegenerative disorder has been suggested [10]. The connection between astrocytes and microglia interaction is still unexplored, neuroinflammation is a key process in understanding the various CNS pathologies, and it is well accepted that both these cell types are involved in very close, dynamic, and continuous crosstalk. This bidirectional communication is crucial in resting, activated, and aged phenotypes, but it the mechanism underlying this is only starting to be explored [25,26]
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